The proposed research is designed to study both in patients and in experimental animals those factors of the lymphoreticulor system which may be involved in the initiation of acute and chronic inflammatory reactions following tissue damage and to assess whether such manifestations may prove to be beneficial in the diagnosis of active myocardial cell necrosis. Clinical trials will be initiated regarding the temporal development incidence and specificity of anti-heart mitochondria autoantibody in a variety of myocardial diseases. In addition, the specificities of autoantibodies developed as a result of other forms of tissue, e.g., hepatocellular necrosis, will be studied with respect to their possible cross-reaction with human heart mitochondria. The second area of study will be to initiate clinical trials to assess the sensitivity of the mitochondrial-dependent consumption of complement components C1, C4 and C2 following myocardial infarction. In addition, the amount of complement consumption will be studied with respect to the severity of the myocardial infarction. The third and fourth portions of the proposed research will be to continue our animal studies in concert with the above mentioned clinical trials. The organelle and organ specificities of anti-heart autoantibodies induced in dogs will be assessed. In addition, attempts will be made to characterize the biochemical nature and stability of the subcellular autoantigens in dog myocardial tissue. The last area of study in the proposed research will be to further characterize the thymic-dependency of the cell-mediated autoimmunity to subcellular organelles. In addition to further elucidating the production of macrophage inhibition factor from isolated leukocytes in tissue culture exposed to various subcellular membranes, the production of other lymphokines such as lymphotoxin and chemotactic factor also will be assessed.